A5076557834- PI3K/AKT/mTOR signaling in cancer
- RNA Research and Splicing
- RNA modifications and cancer
- Retinoids in leukemia and cellular processes
- RNA and protein synthesis mechanisms
- Chronic Lymphocytic Leukemia Research
- Cancer-related gene regulation
- Lymphoma Diagnosis and Treatment
- Protein Degradation and Inhibitors
- HIV/AIDS drug development and treatment
- Biochemical and Molecular Research
- interferon and immune responses
- Mast cells and histamine
- Polyamine Metabolism and Applications
- Acute Lymphoblastic Leukemia research
- CAR-T cell therapy research
- Ubiquitin and proteasome pathways
- Nuclear Structure and Function
- Virus-based gene therapy research
- Genomics and Chromatin Dynamics
- Monoclonal and Polyclonal Antibodies Research
- Acute Myeloid Leukemia Research
- RNA Interference and Gene Delivery
- Viral Infections and Outbreaks Research
- Epigenetics and DNA Methylation
Université de Montréal
2016-2025
Institute for Research in Immunology and Cancer
2015-2024
Polytechnique Montréal
2006-2022
Cornell University
2013
Northwestern University
2013
University of Chicago
2013
BC Cancer Agency
2013
University of Turin
2013
IBM Research - Brazil
2013
Dana-Farber Cancer Institute
2011
We have identified a protein motif, related to the zinc finger, which defines newly discovered family of proteins. The motif was found in sequence human RING1 gene, is proximal major histocompatibility complex region on chromosome six. propose naming this "RING finger" and it 27 proteins, all putative DNA binding functions. synthesized peptide corresponding examined number properties, including metal binding. provide evidence support suggestion that RING finger domain defined
The eukaryotic translation initiation factor eIF4E is deregulated in many human cancers, and its overexpression cells leads to malignant transformation. Oncogenic properties of are directly linked ability bind 7-methyl guanosine the 5′ mRNA. Here, we observe that antiviral analogue ribavirin binds with micromolar affinity at functional site used by mRNA cap, competes eIF4E:mRNA binding, and, low concentrations, selectively disrupts subcellular organization transport mRNAs...
This study demonstrates that the eukaryotic translation initiation factor eIF4E is a critical node in an RNA regulon impacts nearly every stage of cell cycle progression. Specifically, coordinately promotes messenger (mRNA) export several genes involved cycle. A common feature these mRNAs structurally conserved, approximately 50-nucleotide element 3' untranslated region denoted as sensitivity element. sufficient for localization capped to nuclear bodies, formation eIF4E-specific...
Abstract The eukaryotic translation initiation factor eIF4E is dysregulated in a wide variety of human cancers. In the cytoplasm, acts rate-limiting step whereas nucleus, forms nuclear bodies and promotes nucleo-cytoplasmic export subset growth-promoting mRNAs including cyclin D1. only known post-translational modification its phosphorylation at S209. Many studies have examined role on cap-dependent translation. However, no to date explored ability transform cells. Using mutagenesis...
The cysteine-rich zinc-binding motifs known as the RING and B-box are found in several unrelated proteins. Structural, biochemical, biological studies of these reveal that they mediate protein-protein interactions. Several RING-containing proteins oncoproteins recent data indicate proapoptotic activities can be mediated through RING. 1 H NMR methods were used to determine structures RINGs a domain monitor conformational changes undergo upon zinc ligation. This review discusses detail...
The eukaryotic translation initiation factor 4E (eIF4E) acts as both a key and promoter of nucleocytoplasmic transport specific transcripts. Traditionally, its transformation capacity in vivo is attributed to role the cytoplasm. Here, we demonstrate that elevated eIF4E impedes granulocytic monocytic differentiation. Our subsequent mutagenesis studies indicate this block result dysregulated eIF4E-dependent mRNA transport. These RNA function could contribute leukemogenesis. We extended our...
Although aberrant DNA methylation patterning is a hallmark of cancer, the relevance targeting methyltransferases (DNMT) remains unclear for most tumors. In diffuse large B-cell lymphoma (DLBCL) we observed that chemoresistance associated with programming. Prolonged exposure to low-dose DNMT inhibitors (DNMTI) reprogrammed chemoresistant cells become doxorubicin sensitive without major toxicity in vivo. Nine genes were recurrently hypermethylated DLBCL. Of these, SMAD1 was critical...
The eukaryotic translation initiation factor eIF4E is a critical modulator of cellular growth with functions in the nucleus and cytoplasm. In cytoplasm, recognition 5′ m7G cap moiety on all mRNAs sufficient for their functional interaction eIF4E. contrast, we have shown that associates promotes nuclear export cyclin D1, but not GAPDH or actin mRNAs. We determined basis this discriminatory an ∼100-nt sequence 3′ untranslated region (UTR) D1 mRNA, refer to as sensitivity element (4E-SE). found...
The transcription factor PU.1 is an important regulator of hematopoiesis; precise expression levels are critical for normal hematopoietic development and suppression leukemia. We show here that noncoding antisense RNAs modulators proper dosages PU.1. Antisense sense regulated by shared evolutionarily conserved cis -regulatory elements, we can inhibit modulating mRNA translation. propose such will likely be in the regulation many genes may reason large number overlapping complementary...
We have evaluated the eukaryotic translation initiation factor 4E (eIF4E) as a potential biomarker and therapeutic target in breast cancer. eIF4E facilitates nuclear export of specific, growth-stimulatory mRNAs is frequently overexpressed cancer.Breast cancer cells were treated with ribavirin, an inhibitor eIF4E, effects on cell proliferation known mRNA targets determined. expression was assessed, at protein level, lines skin biopsies from patients metastatic disease. Additionally, pooled...
Recognition of the methyl-7-guanosine (m 7 G) cap structure on mRNA is an essential feature metabolism and thus gene expression. Eukaryotic translation initiation factor 4E (eIF4E) promotes translation, export, proliferation, oncogenic transformation dependent this cap-binding activity. eIF4E–cap recognition mediated via complementary charge interactions positively charged m G between negative π-electron clouds from two aromatic residues. Here, we demonstrate that a variant subfamily,...
AbstractThe promyelocytic leukemia zinc finger (PLZF) protein is a transcription factor disrupted in patients with t(11;17)(q23;q21)-associated acute leukemia. PLZF contains an N-terminal BTB/POZ domain which required for dimerization, transcriptional repression, formation of high-molecular-weight DNA-protein complexes, nuclear sublocalization, and growth suppression. X-ray crystallographic data show that the forms obligate homodimer via extensive interface. In addition, dimer possesses...
Antisense oligonucleotides against the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) are able to reduce some forms of apoptosis. In those forms, overall GAPDH levels increase and accumulates in nucleus. The monoamine oxidase B (MAO-B) inhibitor, (-)-deprenyl (DEP), its metabolite (-)-desmethyldeprenyl, a tricyclic DEP analog, CGP3466, can apoptosis independently MAO-B inhibition have been found bind GAPDH. We used neuronally differentiated PC12 cells show that DEP, DES,...
The promyelocytic leukemia protein (PML) forms nuclear bodies which are altered in some disease conditions. We report that the cytoplasmic RNA virus lymphocytic choriomeningitis (LCMV) influences distribution of PML bodies. In cells infected with LCMV, Z and form large primarily cytoplasm. Transient transfection studies indicate alone is sufficient to redistribute cytoplasm colocalize. Coimmunoprecipitation show specific interaction between proteins. A similar result was observed a from...